TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28666	86221;86222;86223	chr2:178560136;178560135;178560134	chr2:179424863;179424862;179424861
N2AB	27025	81298;81299;81300	chr2:178560136;178560135;178560134	chr2:179424863;179424862;179424861
N2A	26098	78517;78518;78519	chr2:178560136;178560135;178560134	chr2:179424863;179424862;179424861
N2B	19601	59026;59027;59028	chr2:178560136;178560135;178560134	chr2:179424863;179424862;179424861
Novex-1	19726	59401;59402;59403	chr2:178560136;178560135;178560134	chr2:179424863;179424862;179424861
Novex-2	19793	59602;59603;59604	chr2:178560136;178560135;178560134	chr2:179424863;179424862;179424861
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-97
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3021
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/I	rs1703111112	None	0.983	N	0.527	0.411	0.450248222533	gnomAD-4.0.0	1.36851E-06	None	None	None	None	N	None	0	2.23624E-05	None	0	0	None	0	0	8.99517E-07	0	0
T/P	rs755715518	-0.538	0.983	N	0.526	0.504	0.44153150616	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
T/P	rs755715518	-0.538	0.983	N	0.526	0.504	0.44153150616	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85876E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.0952	likely_benign	0.0848	benign	-0.728	Destabilizing	0.63	D	0.436	neutral	N	0.475606109	None	None	N
T/C	0.4508	ambiguous	0.3923	ambiguous	-0.307	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
T/D	0.2471	likely_benign	0.2262	benign	0.079	Stabilizing	0.845	D	0.469	neutral	None	None	None	None	N
T/E	0.2683	likely_benign	0.2506	benign	0.008	Stabilizing	0.916	D	0.463	neutral	None	None	None	None	N
T/F	0.3097	likely_benign	0.2613	benign	-1.338	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	N
T/G	0.1924	likely_benign	0.1656	benign	-0.833	Destabilizing	0.845	D	0.48	neutral	None	None	None	None	N
T/H	0.2113	likely_benign	0.1978	benign	-1.337	Destabilizing	0.997	D	0.632	neutral	None	None	None	None	N
T/I	0.398	ambiguous	0.3486	ambiguous	-0.556	Destabilizing	0.983	D	0.527	neutral	N	0.507788921	None	None	N
T/K	0.237	likely_benign	0.2203	benign	-0.259	Destabilizing	0.892	D	0.465	neutral	N	0.520852677	None	None	N
T/L	0.1496	likely_benign	0.1289	benign	-0.556	Destabilizing	0.916	D	0.465	neutral	None	None	None	None	N
T/M	0.1019	likely_benign	0.0967	benign	-0.036	Destabilizing	0.999	D	0.511	neutral	None	None	None	None	N
T/N	0.075	likely_benign	0.0718	benign	-0.032	Destabilizing	0.073	N	0.273	neutral	None	None	None	None	N
T/P	0.4535	ambiguous	0.3801	ambiguous	-0.589	Destabilizing	0.983	D	0.526	neutral	N	0.501712534	None	None	N
T/Q	0.2063	likely_benign	0.1989	benign	-0.382	Destabilizing	0.975	D	0.535	neutral	None	None	None	None	N
T/R	0.2076	likely_benign	0.1936	benign	-0.049	Destabilizing	0.967	D	0.529	neutral	N	0.492127281	None	None	N
T/S	0.0778	likely_benign	0.0726	benign	-0.302	Destabilizing	0.099	N	0.263	neutral	N	0.438156723	None	None	N
T/V	0.2826	likely_benign	0.2429	benign	-0.589	Destabilizing	0.916	D	0.475	neutral	None	None	None	None	N
T/W	0.6517	likely_pathogenic	0.6037	pathogenic	-1.247	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
T/Y	0.2523	likely_benign	0.2185	benign	-0.968	Destabilizing	0.996	D	0.642	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.